A series of new fluorinated diphosphonates, which are related to currently used EHDP and Cl2MDP, will be synthesized by one of two alternate synthetic procedures. It is anticipated that the fluorinated diphosphonate will have many advantages over the EHDP and Cl2MDP and should be therapeutically useful in a variety of dental and medical applications involving calcium disorders. The synthesis permits the preparation of a variety of fluorinated diphosphonate derivatives. Each will be characterized, the Ka values determined, and binding constants with Ca++, Mg++, and Fe+++ will be determined. A high performance liquid chromatographic procedure for the analysis of the diphosphonates will be devised. Two unique experimental procedures to be employed are 19F NMR for detection and characterization of the fluorinated diphosphonates and the use of HPLC to study diphosphonate-hydroxyapatite binding where the hydroxyapatite is the stationary phase. The effectiveness of the fluorinated diphosphonates as inhibitors of bone resorption will be tested first in a bone organ culture assay, which measures resorption by the release of 45Ca from prelabeled bones, and then in the tibial metaphysis of an actively growing rat, a site of active bone remodeling. The inhibitory potencies and histological effects of these compounds will be compared with the extensively studied diphosphonates, EHDP and Cl2MDP. The metabolism and fate of the fluorinated diphosphonates will be studied in both the in vitro and in vivo model systems by determining the concentration of the compound in urine, feces, blood, tibiae, and selected organs and by identifying metabolites. This evaluation of the safety and practicality of the compounds will lay the foundation for their use in treating human diseases of excessive bone resorption.